Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Cell Death Dis. 2018 Feb 5;9(2):155. doi: 10.1038/s41419-017-0197-y.
Hormone therapy drugs, such as bicalutamide and enzalutamide, directed against prostate cancer focus on androgen receptor (AR) signaling and are initially effective, but the disease progresses to lethality as resistance to these drugs develops. A method to prolong the drug response time and improve the drug efficacy is still unavailable. TRIM36 was reported as a novel androgen signaling target gene and is upregulated in prostate cancer. In this study, we found that 63.4% (64/95) of PCa in TMA expressed the TRIM36 protein. Interestingly, patients with negative TRIM36 expression had a shorter biochemical recurrence-free survival. TRIM36 expression was significantly associated with the Gleason score (P = 0.005), delayed prostate cancer cell cycle progression and inhibited cell proliferation in vitro and in vivo, and these effects were mediated via inhibition of the MAPK/ERK phosphorylation pathway. Remarkably, we found that rescuing the expression of TRIM36 during anti-androgen therapy could improve the drug efficacy. Collectively, TRIM36 is a novel androgen-responsive gene, and it dramatically enhanced the efficacy of anti-androgen drugs against prostate cancer.
激素治疗药物，如比卡鲁胺和恩杂鲁胺，针对前列腺癌的雄激素受体（AR）信号，最初是有效的，但随着对这些药物的耐药性的发展，疾病进展为致命性。目前仍缺乏延长药物反应时间和提高药物疗效的方法。TRIM36 被报道为一种新的雄激素信号靶基因，在前列腺癌中上调。在本研究中，我们发现 TMA 中 63.4%（64/95）的前列腺癌表达 TRIM36 蛋白。有趣的是，TRIM36 表达阴性的患者生化无复发生存期更短。TRIM36 表达与 Gleason 评分显著相关（P=0.005），延迟前列腺癌细胞周期进展，并抑制体外和体内的细胞增殖，这些作用是通过抑制 MAPK/ERK 磷酸化通路介导的。值得注意的是，我们发现，在抗雄激素治疗过程中恢复 TRIM36 的表达可以提高药物疗效。综上所述，TRIM36 是一种新型的雄激素反应基因，它显著增强了抗雄激素药物对前列腺癌的疗效。
